Antibody variable region glycosylation: biochemical and clinical effects

ConclusionsThere is a substantial body of evidence that implicates antibody glycosylation in disease. Several reports have documented that the presence of carbohydrate in the variable region contributes to alterations in protein solubility, leading to formation of immune complexes or tissue deposition. It has been suggested that disruptions in the regulation of glycosylation can lead to the expression of altered carbohydrate structure (such as agalactosyl sugars) with the resulting glycoproteins exhibiting properties (such as a tendency towards aggregation) that contribute to disease [40].The conservation of a potential glycosylation site in many anti-carbohydrate antibodies in the VH gene at Asn 58 suggests that, for this group of antibodies, the presence of carbohydrate may contribute to antigen binding. For anti-dextrans, it has been demonstrated that the presence of carbohydrate at this site enhances antigen affinity, but that even slight differences in the position of the carbohydrate attachment site in CDR2 result in quite different outcomes. This system will prove useful to study the contribution of V region-associated carbohydrate to the antigen-combining site.

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